National Vector Muscular Dystrophy Core

国家矢量肌营养不良症核心

• 批准号: 7535878
• 负责人: Jeffrey Beecham
• 金额: $ 31.11万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-05 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7535878
• 关键词: Adenoviruses; Award; Basic Science; Canis familiaris; Cells; Clinic; Clinical; Clinical Protocols; Clinical Research; Clinical Trials; Contracts; Cyclic GMP; Dependovirus; Development; Duchenne muscular dystrophy; Effectiveness; Ensure; Environment; Floor; Gene Transfer; Genes; Goals; Guidelines; Health Services Research; Hospitals; Human; Immune Targeting; Information Management; Information Systems; Information Technology; Joints; Laboratories; Laboratory Study; Lentivirus Vector; Letters; Manufacturer Name; Medical; Methods; Modeling; Monkeys; Muscular Dystrophies; Neurosciences; Non-Viral Vector; Numbers; Operative Surgical Procedures; Patients; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Plasmid Cloning Vector; Plasmids; Policies; Procedures; Process; Production; Quality Control; Range; Regulation; Relative (related person); Report (document); Reporting; Research; Research Design; Research Infrastructure; Research Personnel; Resource Development; Resources; Retroviridae; Safety; Serotyping; Services; Site; Source; Speed; Staging; Standards of Weights and Measures; Structure; Study Section; Subfamily lentivirinae; System; Technology; Test Result; Testing; Time; Translational Research; Translations; United States Food and Drug Administration; United States National Institutes of Health; Viral; Wing; adeno-associated viral vector; base; cell bank; cost; cost effective; design; drug development; expectation; experience; gene therapy; improved; manufacturing process; patient safety; pre-clinical; pre-clinical research; programs; research and development; research study; scale up; success; vector; wasting

There is good evidence that gene therapy may be an effective new way to treat muscular dystrophy. However, the :echnologies and information required to bring these therapies into standard medical practice remain to be developed. The goal of this proposal is to provide the Wellstone program with a Scientific Research Resource Core that will facilitate the rapid and safe delivery of clinical studies that will establish gene therapies value for the treatment of muscular dystrophy. One of the keys to rapidly bringing new research developments into the clinic is to effectively manage the flow of information and technologies during translational research. Numerous pitfalls, delays, and unanticipated problems are encountered during translational research, and without effective methods of avoiding them, progress is significantly slowed and becomes much more costly. For example, without effective technology management, the drug development process is slowed when the technology transitions from the basic research lab into early Process Development and scale-up for safety testing. Likewise, effective information management is crucial to quickly transition from the minimally-regulated, research environment into the highly regulated processes of drug manufacturing, safety testing, and clinical trials. Effective information management is also important in speeding the regulatory approval process through a range of Local and Federal agencies. Lastly, the technology and information must integrate into a clinical study for actual patient treatments to begin. Ineffective information and technology management at any of these transition points can endanger patient safety and significantly delay the entire drug development process. The UNC Joint Vector Laboratories are structured and organized so as to streamline the flow of technologies and drug development information. Our previous experiences in vector design, development, and production have allowed us to develop new organizational and operational paradigms. These new paradigms have a proven record of effectiveness as shown by our success in getting a Phase I study for Duchene's Muscular Dystrophy into clinical trials safely and within a very short period of time. Through this experience, and others, we have found that the key requirements are: 1) The ability to manufacture vectors in an efficient and cost effective manner, 2) Having standardized procedures in place for coordinating the activities of the investigator, the trial Sponsor, the drug manufacturer, and the various testing sites, 3) Having the expertise to make sure that the vectors used for pre-clinical and clinical studies meet specific standards of biologic quality (viral liter, infectivity, and purity), 4) Having the expertise to make sure the vectors used for pre-clinical and clinical studies meet the required drug safety standards and specifications, and 5) Having the regulatory expertise to be able to provide investigators with information and guidance so they can rapidly meet all regulatory expectations and can submit successful IND applications on their first attempt. In this proposal we outline the facilities, programs, and processes that we have created that have allowed us to rapidly develop clinical protocols. These are the procedures that we routinely now use to streamline the translational process and to ensure product and patient safety. In addition, we describe how we have integrated the manufacturing processes for the different stages of translational research and how we use this approach to provide investigators with a comprehensive assortment of research resources that they can use throughout the development of their research program. In the Preliminary Studies section, we describe how we have applied these technologies and quality contra programs to previous production campaigns for DMD. We also discuss new programs that we are currently developing that are designed to further enhance our ability to speed the drug development, manufacturing, and testing processes In the Research Design section we describe how we plan to provide these various technologies, information systems and drug development programs to MD investigators who will use our facilities as a Scientific Research Resource Core.

有充分的证据表明，基因治疗可能是治疗肌营养不良症的有效方法。但是， ：将这些疗法带入标准医学实践所需的技术和信息尚待开发。 该提案的目的是为Wellstone计划提供科学的研究资源核心 促进临床研究的快速，安全交付，以确定基因疗法的价值 肌肉营养不良。快速将新的研究发展带入诊所的关键之一是有效 管理转化研究过程中信息和技术的流动。许多陷阱，延误和 在翻译研究中遇到意外问题，没有有效的方法避免它们， 进度大大放缓，变得更加昂贵。例如，没有有效的技术 管理，当技术从基础研究实验室转变为 早期过程开发和安全测试的扩大规模。同样，有效的信息管理对 快速从最小调节的研究环境过渡到高度调节的药物过程 制造，安全测试和临床试验。有效的信息管理对于加速也很重要 通过一系列地方和联邦机构的监管批准过程。最后，技术和信息 必须整合到临床研究中才能开始实际的患者治疗。无效的信息和技术 在任何这些过渡点的管理中的管理都会危害患者的安全，并大大延迟整个药物 发展过程。 UNC联合矢量实验室的结构和组织，以简化​​技术和药物的流动 开发信息。我们以前在向量设计，开发和生产方面的经验使我们得以 开发新的组织和运营范例。这些新范式具有可靠的有效性记录 正如我们在获得I阶段I研究中的成功研究所表明的那样，安全地进入临床试验，并 在很短的时间内。通过这种经验，我们发现关键要求是： 1）以高效且具有成本效益的方式制造向量的能力，2）在 协调调查员，试验发起人，药品制造商和各种测试活动的活动的场所 站点，3）具有专业知识以确保用于临床前和临床研究的向量符合特定 生物学质量标准（病毒升，感染力和纯度），4）拥有专业知识以确保向量用于 临床前和临床研究符合所需的药物安全标准和规格，5）具有调节性 能够为调查人员提供信息和指导的专业知识，以便他们可以迅速满足所有监管 期望并可以在首次尝试时提交成功的IND申请。 在此提案中，我们概述了我们创建的设施，程序和流程，这些设施和流程使我们能够迅速 制定临床方案。这些是我们现在通常使用的过程来简化翻译过程 并确保产品和患者安全。此外，我们描述了如何整合制造业 转化研究不同阶段的过程以及我们如何使用这种方法为研究人员提供 他们可以在整个研究的开发过程中使用的全面研究资源 程序。在“初步研究”部分中，我们描述了我们如何应用这些技术和质量的矛盾 DMD先前生产活动的计划。我们还讨论我们目前正在开发的新程序 旨在进一步增强我们加快药物开发，制造和测试过程的能力 在研究设计部分中，我们描述了如何计划提供这些各种技术，信息系统 以及将使用我们的设施作为科学研究资源核心的医学博士调查人员的药物开发计划。